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Objective: Neuroblastoma (NB) is a type of extracranial solid tumor that usually occurs in children. Drug resistance has become a major obstacle in NB chemotherapy. Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) is an oncogene in many cancers, including NB. This study aimed to investigate the role of SNHG7 in cisplatin sensitivity of NB and the underlying mechanism., Patients and Methods: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and the IC50 of cisplatin was calculated. The protein levels of autophagy markers were measured by Western blot assay. The levels of SNHG7, miR-329-3p and myosin X (MYO10) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The interaction among SNHG7, miR-329-3p and MYO10 was confirmed by Dual-Luciferase reporter assay., Results: Cisplatin curbed the viability of NB cells in a dose-dependent manner and facilitated autophagy in NB cells. Silencing of SNHG7 reduced cisplatin resistance and suppressed cisplatin-induced autophagy. SNHG7 was a sponge of miR-329-3p and modulated chemosensitivity and autophagy by regulating miR-329-3p. In addition, SNHG7 upregulated MYO10 by sponging miR-329-3p. MYO10 restored the effect of miR-329-3p on cisplatin sensitivity and autophagy. Moreover, suppression of autophagy blocked SNHG7-induced cisplatin resistance., Conclusions: Depletion of SNHG7 potentiated cisplatin sensitivity through inhibition of autophagy by modulating miR-329-3p/MYO10 axis, providing a new therapeutic approach to overcome cisplatin resistance in NB chemotherapy.

Objective: Diabetic nephropathy (DN) is one of the primary complications of diabetes. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) has been established to function in DN, while its role in high glucose (HG)-induced human mesangial cells (HMCs) remains limited., Materials and Methods: The expression level of CASC2 and miR-133b was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay. Extracellular matrix (ECM) accumulation was monitored through the expression levels of collagen IV (Col IV) and fibronectin (FN) using qRT-PCR and western blot analyses. Oxidative stress was observed through the expression of NADPH oxidase2 (NOX2) and the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) using western blot or corresponding detection kit. The expression of forkhead box P1 (FOXP1) at mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. The relationship between miR-133b and CASC2 or FOXP1 was predicted by online bioinformatics tools and verified by dual-luciferase reporter assay or RNA pull-down., Results: The expression of CASC2 was reduced in serum from DN patients and HG-induced HMCs. CASC2 upregulation inhibited HG-induced HMCs proliferation, ECM accumulation and oxidative stress. MiR-133b was a target of CASC2 with a high level in serum from DN patients and HG-induced HMCs, and its enrichment reversed the effects of CASC2 upregulation. Besides, FOXP1 was a target of miR-133b with a low level in HG-induced HMCs, and its knockdown abolished the impacts of CASC2 upregulation., Conclusions: CASC2 upregulation suppressed HG-induced proliferation, ECM accumulation and oxidative stress of HMCs through miR-133b /FOXP1 regulatory axis, suggesting that CASC2 was a novel biomarker for DN treatment.

Objective: The aim of this study was to investigate the effect of micro-ribonucleic acid (miR)-130a on neuronal injury in rats with intracerebral hemorrhage (ICH) through the phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway., Materials and Methods: A total of 30 healthy male rats were randomly divided into three groups, including the blank control group, ICH model group (ICH group) and ICH model + miR-130a treatment group (miR-130a treatment group). The differences in neurological injury, the number of apoptotic cells in brain tissues, the activity of Caspase-9 and protein expressions of PTEN/PI3K/AKT were analyzed among the three groups, respectively., Results: Neurological function was normal without injury in the control group. However, the neurological injury was severe in the ICH group and mild in the miR-130a treatment group. There were statistically significant differences in neurological function in the control group relative to those of the ICH group and miR-130a treatment group (p<0.05). Meanwhile, the neurological injury was markedly milder in the miR-130a treatment group than that of the ICH group, showing a statistically significant difference (p<0.05). The number of apoptotic cells was remarkably smaller in the control group when compared with the ICH group and miR-130a treatment group. However, it was markedly larger in the ICH group than that of the miR-130a treatment group, showing significant differences (p<0.05). The activity of Caspase-9 was significantly lower in the control group than ICH group and miR-130a treatment group (p<0.05). However, it increased remarkably in the ICH group compared with that of the miR-130a treatment group (p<0.05). Moreover, the protein level of PTEN in the ICH group was significantly higher than control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, no marked difference in the protein level of PTEN was observed between the control group and miR-130a treatment group (p>0.05). The protein levels of the phosphorylated 3-hydroxy kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) were remarkably lower in the ICH group than those of the control group and miR-130a treatment group, displaying statistically significant differences (p<0.05). However, they were remarkably higher in the miR-130a treatment group than that of the control group (p<0.05)., Conclusions: MiR-130a promotes neuronal growth in brain tissues in ICH rats and alleviates neuronal injury after ICH through the PTEN/PI3K/AKT signaling pathway. Our findings suggest that miR-130a exerts important clinical significance in the treatment of ICH.

Objective: To clarify the influence of microRNA-93-5p (miRNA-93-5p) on biological behaviors of gastric cancer (GC) cells and its regulatory effect on Hippo pathway., Materials and Methods: SGC-7901 and HGC-27 cells were used for establishing miRNA-93-5p overexpression and downregulation model through transfection of miRNA-93-5p mimics or inhibitor, respectively. Relative levels of genes in Hippo pathway were determined in GC cells transfected with miRNA-93-5p mimics or inhibitor by quantitative Real-time polymerase chain reaction (qRT-PCR). Regulatory effects of miRNA-93-5p on proliferative, migratory and invasive abilities of GC cells were evaluated by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively., Results: MiRNA-93-5p was markedly upregulated by transfection of miRNA-93-5p mimics into SGC-7901 cells, which was downregulated by transfection of miRNA-93-5p inhibitor into HGC-27 cells. Overexpression of miRNA-93-5p accelerated GC cells to proliferate, migrate and invade. Meanwhile, miRNA-93-5p overexpression in GC cells upregulated downstream genes in Hippo pathway, including CDX2, FOXM1 and CTGF., Conclusions: MiRNA-93-5p enhances proliferative, migratory and invasive abilities of GC cells by activating Hippo pathway, which may serve as a diagnostic and therapeutic target for GC.

Objective: Our study aims to explore whether microRNA-940 could participate in early abortion by inhibiting placenta implantation and its underlying mechanism., Patients and Methods: Expressions of microRNA-940 and ZNF672 in the placental villi of 6 early abortion pregnancies and 6 normal pregnancies were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Expressions of microRNA-940 and ZNF672 in trophoblast cells (BeWo, JEG3, Wish and HTR-8) were also detected. Cell counting kit-8 (CCK-8) assay was performed to detect the effect of microRNA-940 on the proliferation of trophoblast cells after being transfected with microRNA-940 inhibitor or mimics, respectively. Dual-Luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay were conducted to demonstrate the binding condition of microRNA-940 to ZNF672., Results: MicroRNA-940 was highly expressed in placental villi of early abortion pregnancies, whereas ZNF672 was lowly expressed. HTR-8 cells expressed the highest level and BeWo cells expressed the lowest level of microRNA-940. After transfection of microRNA-940 inhibitor in HTR-8 cells, the proliferative capacity was remarkably increased. On the contrary, the transfection of microRNA-940 mimic downregulated the proliferation of BeWo cells. Dual-Luciferase reporter gene assay demonstrated that microRNA-940 targets ZNF672. RIP results further indicated that microRNA-940 binds to ZNF672., Conclusions: MicroRNA-940 is highly expressed in the placental villi of early abortion pregnancies and promotes the occurrence of early abortion by inhibiting the proliferation of trophoblast cells by targeting ZNF672.

Objective: To investigate whether lncRNA H19 can regulate NF1 expression through competitive binding to microRNA-107, thereby participating in the occurrence and development of non-small cell lung cancer (NSCLC)., Patients and Methods: Expression levels of H19 and NF1 in NSCLC tissues, paracancerous tissues and NSCLC cell lines were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The binding condition of microRNA-107, H19 and NF1 was detected by dual-luciferase reporter gene assay. Corresponding lentiviruses of H19 were constructed. The regulatory effects of H19 on proliferative and migratory abilities of A549 cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. Rescue experiments were conducted to explore the regulatory interaction between H19 and microRNA-107 in A549 cells., Results: H19 and NF1 were highly expressed in NSCLC tissues and NSCLC cell lines (A549 and HCC823) than those of controls. Overexpressed H19 increased proliferative and migratory abilities of A549 cells. Dual-luciferase reporter gene assay demonstrated that H19 regulates NF1 expression through competitive binding to microRNA-107, thereafter participating in NSCLC development., Conclusions: H19 is highly expressed in NSCLC, which promotes NSCLC development by regulating NF1 via competitive binding to microRNA-107.

Objective: To investigate the association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma (HCC). Methods: PubMed, Web of Science, Cochrane Library, Wanfang Data, and Google Scholar were searched for case-control studies on the association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC published up to October, 2016 in Chinese or English. The Q-statistics test was used to evaluate the heterogeneity of these articles. Results: A total of 18 articles with 5 610 cases and 7 531 controls were included for the meta-analysis. There was no significant association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC. The odds ratio ( OR ), 95% confidence interval (95% CI ), and P values for the five genetic models were as follows: the allele model C/G ( OR = 0.99, 95% CI 0.88-1.06, P = 0.440); the heterozygous model CG/GG ( OR = 0.99, 95% CI 0.90-1.10, P = 0.898); the homozygous model CC/GG ( OR = 0.91, 95% CI 0.75-1.10, P = 0.314); the dominant model CC+CG/GG ( OR = 0.97, 95% CI 0.79-1.19, P = 0.759); the recessive model CG+GG/CC ( OR = 1.05, 95% CI 0.94-1.18, P = 0.405). A subgroup analysis of race, source of control population, and Hardy-Weinberg equilibrium were performed in these five genetic models, and miR-146a single nucleotide polymorphism increased the susceptibility to HCC only in the control population-based subgroups of the recessive model CG+GG/CC ( OR = 1.20, 95% CI 1.02-1.40, P = 0.024). There was no association between miR-146a rs2910164 polymorphism and susceptibility to HCC in all the other subgroups. A stratified analysis of HBV infection revealed that miR-146a rs2910164 polymorphism increased the risk of HBV-positive HCC ( OR = 1.26, 95% CI 1.10-1.49, P = 0.001). Conclusion: There is no significant association between miR-146a rs2910164 polymorphism and the risk of HCC, but miR-146a rs2910164 polymorphism may increase the risk of HBV-positive HCC.

Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS., (© 2017 British Society for Immunology.)

Hepatocellular carcinoma is one of the most common malignant tumors worldwide; it is estimated that there were 782,000 new cases in 2012. MicroRNAs (miRNAs) play an important role in carcinogenesis by regulating oncogenes and tumor suppressors. We investigated the role of miR-146a, miR-196a2, and miR-499 polymorphisms in the risk of hepatocellular carcinoma in a Chinese population. Hepatocellular carcinoma patients (175) and healthy controls (302) were recruited between April 2013 and March 2015. Genotype analysis of miR-146a, miR-196a2, and miR-499 polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism. There was a significant difference between the genotype distribution of miR-196a2 in hepatocellular carcinoma patients and controls (X 2 = 17.23, P < 0.001). CG and GG miR-146a genotypes significantly elevated the risk of hepatocellular carcinoma compared with the CC genotype, with adjusted ORs (95%CI) of 3.05 (1.07-8.70) and 4.96 (1.64-14.97), respectively. In the recessive model, the CG + GG genotype had a 3.75-fold risk of hepatocellular carcinoma compared with the CC genotype, with an adjusted OR (95%CI) of 3.75 (1.39-10.11). However, no significant association was observed between miR-196a2 and miR-499 variants and risk of hepatocellular carcinoma in the co-dominant, dominant, and recessive models. The miR-146a polymorphism is a G to C substitution that causes a mismatch in the stem-loop of miRNA, which influences how the expression and transcriptional regulation of miRNA affects its target genes. Our study revealed that the GG and CG genotypes of miR-146a increased the risk of hepatocellular carcinoma in the Chinese population., Competing Interests: The authors declare no conflict of interest.

MicroRNAs (miRNAs) are one of a growing class of noncoding RNAs that are involved in the regulation of a wide range of metabolic processes including cellular differentiation, cell proliferation and apoptosis. The generation of miRNA is regulated in complex ways, for example by small interfering RNAs (small nucleolar and nuclear RNAs) and various other metabolites. This complexity of control is likely to explain how a relatively small part of the DNA that codes for proteins has enabled the evolution of such complex organisms as mammals. Non-protein-coding DNA is therefore thought to carry the memory of early evolutionary steps that led to progressively complex metabolic controls. Clinically, miRNAs are becoming increasingly important following the recognition that some congenital abnormalities can be traced to defects in miRNA processing. The potential for manipulating metabolism and affecting disease processes by the pharmaceutical or biological targeting of specific miRNA pathways is now being tested. miRNAs are also released into the extracellular milieu after packaging by cells into nano-sized extracellular vesicles. Such vesicles can be taken up by adjacent and possibly more distant cells, thereby allowing coordinated intercellular communication in specific tissues. Extracellular miRNAs found in the blood stream may also serve as novel biomarkers for both diagnosing specific forms of cancer and assessing the likelihood of metastasis, and as powerful prognostic indices for various cancers. Here, we discuss the role of intracellular and extracellular miRNAs in nutritional control of various (patho)physiological processes. In this review, we provide an update of the presentations from the 25th Marabou Symposium (Stockholm, 14-16 June 2013) entitled 'Role of miRNA in health and nutrition', attended by 50 international experts, (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Expression of apoptotic protease activating factor-1 (Apaf-1) gradually decreases during brain development, and this decrease is likely responsible for the decreased sensitivity of brain tissue to apoptosis. However, the mechanism by which Apaf-1 expression is decreased remains elusive. In the present study, we found that four microRNAs (miR-23a/b and miR-27a/b) of miR-23a-27a-24 and miR-23b-27b-24 clusters play key roles in modulating the expression of Apaf-1. First, we found that miR-23a/b and miR-27a/b suppressed the expression of Apaf-1 in vitro. Interestingly, the expression of the miR-23-27-24 clusters in the mouse cortex gradually increased in a manner that was inversely correlated with the pattern of Apaf-1 expression. Second, hypoxic injuries during fetal distress caused reduced expression of the miR-23b and miR-27b that was inversely correlated with an elevation of Apaf-1 expression during neuronal apoptosis. Third, we made neuronal-specific transgenic mice and found that overexpressing the miR-23b and miR-27b in mouse neurons inhibited the neuronal apoptosis induced by intrauterine hypoxia. In conclusion, our results demonstrate, in central neural system, that miR-23a/b and miR-27a/b are endogenous inhibitory factors of Apaf-1 expression and regulate the sensitivity of neurons to apoptosis. Our findings may also have implications for the potential target role of microRNAs in the treatment of neuronal apoptosis-related diseases.

Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer. By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread disruption of miRNA expression during colorectal tumorigenesis. In particular, among a panel of presumed targets generated by in silico analysis that may interact with these aberrantly expressed miRNAs, KRAS oncogene has been further experimentally validated as the target of miR-143. First, an inverse correlation between KRAS protein and miR-143 in vivo was found. Second, KRAS expression in Lovo cells was significantly abolished by treatment with miR-143 mimic, whereas miR-143 inhibitor increased KRAS protein level. Third, luciferase reporter assay confirmed that miR-143 directly recognize the 3'-untranslated region of KRAS transcripts. Four, Lovo cells treated with miR-143 inhibitor showed a stimulated cell proliferation, whereas miR-143 overexpression had an opposite effect. Finally, inhibition of KRAS expression by miR-143 inhibits constitutive phosphorylation of ERK1/2. Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation.